Table 3 The three component reactions of aldehydes, aniline and triethyl
phosphite in [bmim][PF6] in the presence of Sc(OTf)3 as catalyst
The three component reactions of various aldehydes and
aniline with P(OEt)3 in the presence of 1 mol% Sc(OTf)3 in
ionic liquid, [bmim][PF6], gave the corresponding a-amino
phosphonates in excellent yields as shown in Table 3.
In summary, the catalytic activities of various lanthanide
triflates as well as indium trichloride were examined for the
three component reactions of aldehydes, amines and phospho-
rus nuleophiles, HP(O)(OEt)2 and P(OEt)3, in room temperature
ionic liquids. The catalytic activities were very dependent on the
counter anion, X, as well as on the phosphorus nucleophile. The
catalysts immobilized on ionic liquid can be reused several
times without any loss of activity.
Entry
Aldehyde
Yield (%)a
1
2
3
Benzaldehyde
p-Methoxybenzaldehyde
o-Tolualdehyde
97
> 99
90
4
5
6
7
8
9
10
m-Tolualdehyde
p-Tolualdehyde
> 99
> 99
93
97
> 99
93
p-Fluorobenzaldehyde
a,a,a-Trifluoro-p-tolualdehyde
1-Naphthaldehyde
3-Thiophenecarboxaldehyde
3-Furaldehyde
Notes and references
90
† General procedure for the three component reactions and catalyst
recycling: aniline (0.25 mmol), an aldehyde (0.25 mmol) and a phosphorus
nucleophile, HP(O)(OEt)2 (1 mmol) or P(OEt)3 (1 mmol), were succes-
sively added to a solution of catalyst (0.25 3 1022 mmol) in an ionic liquid
(1 mL) at 20 °C. The mixture was stirred at the same temperature for 27 h
for HP(O)(OEt)2 or 2 h for P(OEt)3. The mixture was extracted with
a
Isolated yield
the reaction. The counter anion of the ionic liquids affected the
catalytic activity considerably (entries 9–11), thus, only 18% of
product was obtained upon using BF4 anion (entry 10 in Table
benzene (4 mL
3 5) and concentrated. Purification by silica gel
chromatography afforded the desired product. More reactants (aldehyde,
aniline and P(OEt)3) were added to the ionic liquid solution remaining in the
vessel. This was the start of the second cycle.
1). By employing indium trichloride as
a catalyst in
[bmim][PF6], the reaction also proceeded efficiently (entry 12
in Table 1). However, the reaction in dichloromethane solvent
using Sm(OTf)3 afforded product only in 70% yield (entry 13 in
Table 1).
1 P. Wasserscheid and W. Keim, Angew. Chem., Int. Ed., 2000, 39, 3772;
T. Welton, Chem. Rev., 1999, 99, 2071; K. R. Seddon, J. Chem.
Technol. Biotechnol., 1997, 68, 351; Y. Chauvin and H. Olivier,
CHEMTECH, 1995, 26; and references therein.
2 C. Chiappe, D. Capraro, V. Conte and D. Pieraccini, Org. Lett., 2001, 3,
1061.
3 C. E. Song and E. J. Rho, Chem. Commun., 2000, 837.
4 R. A. Brown, P. Pollet, E. McKoon, C. A. Eckert, C. L. Liotta and P. G.
Jessop, J. Am. Chem. Soc., 2001, 123, 1254.
5 P. Kafarski and B. Lejczak, Phosphorous Sulfur Silicon, 1991, 63, 193;
and references therein.
6 C. Qian and T. Huang, J. Org. Chem., 1998, 63, 4125.
7 B. C. Ranu, A. Hajira and U. Jana, Org. Lett., 1999, 1, 1141.
8 K. Manabe and S. Kobayashi, Chem. Commun., 2000, 669.
9 S. Kobayashi, Synlett, 1994, 689; W. Xie, Y. Jin and P. G. Wang,
CHEMTECH, 1999, 29, 23.
We expected that employing triethyl phosphite, P(OEt)3, as a
phosphorus nucleophile could overcome the drawback of
catalyst recycling in the three component reactions. Mechanist-
ically, the water generated during formation of imine could be
used for the hydrolysis of phosphonium intermediate10 to give
a-amino phosphonates and EtOH as shown in Scheme 1.
The use of P(OEt)3 instead of HP(O)(OEt)2 changed the
catalytic activities of the lanthanide triflates. In this reaction
system, Sc(OTf)3 exhibited the highest catalytic activity (97%,
entry 1 in Table 2), and the reaction was completed within 2 h.
The Sc(OTf)3 can be used five times without any loss of
catalytic activity (entry 1 in Table 2). In second cycle reactions,
as we expected, the catalytic activities of the recovered catalysts
except InCl3 (entry 5 in Table 2) were almost retained.
10 In ref. 8, Kobayashi stated that the phosphonium intermediate was
hydrolyzed rapidly in water as solvent.
Chem. Commun., 2001, 1698–1699
1699
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